WO1987002867A1 - Hydrolyzed protein chelates - Google Patents
Hydrolyzed protein chelates Download PDFInfo
- Publication number
- WO1987002867A1 WO1987002867A1 PCT/US1986/002193 US8602193W WO8702867A1 WO 1987002867 A1 WO1987002867 A1 WO 1987002867A1 US 8602193 W US8602193 W US 8602193W WO 8702867 A1 WO8702867 A1 WO 8702867A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- protein
- mineral nutrient
- enzyme
- hydrolyzed
- magnesium
- Prior art date
Links
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- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000004836 empirical method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000011773 ferrous fumarate Substances 0.000 description 1
- 229960000225 ferrous fumarate Drugs 0.000 description 1
- 235000002332 ferrous fumarate Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229940066779 peptones Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 230000007065 protein hydrolysis Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23J—PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
- A23J3/00—Working-up of proteins for foodstuffs
- A23J3/30—Working-up of proteins for foodstuffs by hydrolysis
- A23J3/32—Working-up of proteins for foodstuffs by hydrolysis using chemical agents
- A23J3/34—Working-up of proteins for foodstuffs by hydrolysis using chemical agents using enzymes
Definitions
- This invention relates to nutritional chemistry and, in particular, to the methods of preparing metal-protein chelates.
- Rational nutritional supplementation is an evolving concern of responsible consumers. More and more, we make a conscious effort to "do right" by our bodies.
- Chelated minerals particularly those identified as amino-acid chelates or chelates created with hydrolzyed vegetable protein, have been demonstrated to possess beneficial nutritional and therapeutic properties when compared to conventional mineral forms such as oxides,
- Proteins, fats and carbohydrates form the three traditional classes of food. Fats and carbohydrates supply energy while proteins furnish certain essential components containing nitrogen and sulfur which make up a major part of human and animal cellular protoplasm.
- Hydrolytic and enzymatic degradation of the molecules occur in the stomach, duodenum and jejunum with 35 some degradation also occurring in the ileum. Microbial degradation occurs in the ileum and colon. Complexation and mucin binding occur in the stomach, duodenum and jejunum. Passive diffusion and active transport occur in all of these digestive organs.
- R radical determines the name and characteristics of the amino acid.
- the principal amino acids are glycine, alanine, valine, leucine, isolucine, - -. serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, arginine, cysteine, cystine, methionine, phenyalalanine, tyrosine, tryptophan, histidine, proline and hydroxyproline.
- a pH of at least 7.5 and preferrably from ph 8 to pH 10 is specified by Ashmead, et al.
- Ashmead et al.
- the optimum pH for the formation of a genuine amino acid chelate is 7.0 ⁇ 0.05, i.e. neutral.
- the intracellular fluid of the cells is very much different than the extracellular fluid (Guyton, A. , Basic Human Physiology, 1971, P 37).
- the extracellular fluid contains large quantities of sodium 142 meq/1 while the intracellular fluid contains only 10 meq/1.
- the pH of the intracellular fluid is 7.0 while that of extracellular fluid is 7.4.
- a multi mineral chelated tablet for oral dosage is manufactured by the following: 10,000 tablet batch
- the procedure involves mixing the mineral salts in a wet mixer - granulator for 20-30 minutes, then adding the barley protein isolate and mixing for another 20 minutes.
- the mix is then wetted with deionized distilled water to a slurry-like texture;, the pH is measured which is usually slightly acidic about 6.0, then adjusted to pH 7.0 with 0.1N sodium hydroxide, using water as the wetting agent as the need may be to a final wet mix.
- the material is spread on trays, dried in an oven to 25°C for 3 days, ground up, mixed with excipients and tabletted according to certain preset specifications.
- Infra-red spectroscopic tracings of the multi-mineral hydrolyzed barley protein chelate shows very prominent and conspicuous abosrption peaks completely different than the tracings of the individual metal salts used as starting materials in the chelating process.
- Enzymes are very effective in small amounts and they remain unchanged after the reaction takes place, but the drawbacks to this process is the sensitivity of the enzyme to temperature, pH, and salt concentrations which affect their stability and the cost for its commercial application since the enzymes are very expensive to buy and maintain their activity.
- the ionization state which affects the activity of the enzyme is pH dependent; thus, the enzymatic chelation process is pH sensitized.
- the enzymatic chelation process depends on two factors:
- K is the equilibrium constant.
- an equilibrium constant is achieved when the concentration ratio of the reactants is at equilibrium.
- the K depends on the pH and temperature to get a full range amino acid chelation.
- pH is optimize at 7.0 and temperatures at 25°C, which is low heat, endo-thermal, to form a biologically active hydrolyzed protein chelate, that can be easily absorbed and assimilated through the gastro-intestinal tract.
- a zinc sulfate molecule dissociated into zinc and sulfate molecules that are positively and negatively charged respectively
- Enzymatic Activity This is measured by determining the amount of substrate ion converted per unit time.
- the enzyme for which the metabolite is a substrate dictates that the reaction goes to completion in which case the metabolite is converted completely.
- Enzyme reactions are associated with cellular membranes. Sugars are transported into yeast cells by a mechanism involving phosphorylatin by enzymes located in the cell surface. That is to say that newly formed enzymes contain carbons arising from amino acids synthesized subsequent to addition of an inducer and utilization of the individual amino acids is simultaneous, rather than by stepwise synthesis of longer chain molecules. With this principle in mind, it is relevant to recall that minerals may activate enzyme formation and separation by forming chelates or complexes, with different kinds of proteins. Magnesium interacts with purines and pyrimidines to form chelate rings, which in turn may become part of enzyme systems, for example.
- Calcium carbonate and Magnesium Oxide are mixed thoroughly with deionized distilled water, to a wet finish and kept in a mixer.
- soy protein isolate which is 25% by weight of the salt mix is wetted with dionized, distilled water, the pH is adjusted to 7.0 with 0.1N sodium hydroxide and an equal amount of Pepsin N.F. powder is mixed with it, spread on trays and put in an oven at 25 C for 18 hours.
- the hydrolyzed soy protein is then added to the Calcium/Magnesium wet mix, deionized distilled water is added if the need may be, mixed thoroughly for about 30 minutes and spread on trays and let to dry in an oven at 25°C for about three days.
- the dry material is oscillated, mixed with excipients and tableted according to conventional specifications.
- Calcium, magnesium, vanadium, manganese, copper, cobalt, iron and zinc are metals which various valancies in the periodic chart can be chelated and rendered bioavailable to the cellular epithelium.
- Selenium although belongs to the non-metal group with three different valancies it can be bound biologically to yeast by an enzymatic process.
- chromium belongs to the metal group with valancies of 2, 3 and 6, yet can be biologically bound to yeast by an enzymatically active process or geniunely chelated.
- Minerals are usually activators of enzyme synthesis or formation processes and in accord with the law of equilibrium of aqueous solutions, diffusion of solvent occurs from the hypotonic to the hypertonic medium which is influenced by the presence of other ions which compete for a position in the membrane surface causing a competitive inhibition process of some elements that are crucial to the metabolism of the cell.
- various amino acids are transported in descending order of efficiency as follows: L-Valine, L-Alanine, Glycine, L-Arginine, dl-Phenylalanine. This entices one to take into consideration the type of protein to use in forming chelates, knowing the absorption coefficient of each.
- This invention is useful in the manufacture of food supplements for human and animal useage.
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An endothermal, low temperature process for preparing hydrolyzed protein chelates at neutral pH, chemically or biologically resulting in a chelate which is more easily absorbed and assimilated through the gastro-intestinal tract.
Description
HYDROLYZED PROTEIN CHELATES Field of the Invention
This invention relates to nutritional chemistry and, in particular, to the methods of preparing metal-protein chelates.
Background of the Invention Rational nutritional supplementation is an evolving concern of responsible consumers. More and more, we make a conscious effort to "do right" by our bodies.
10. Chelated minerals, particularly those identified as amino-acid chelates or chelates created with hydrolzyed vegetable protein, have been demonstrated to possess beneficial nutritional and therapeutic properties when compared to conventional mineral forms such as oxides,
15 gluconates, citrates, sulfates. (Ashmead, U.S. Patent No., 4,020,158).
Morgan and Drew used the term "chelates" as derived from the word "chele" meaning crab's claw. (J. Chem. Soc. .117,1456 [1920]).
20 Proteins, fats and carbohydrates form the three traditional classes of food. Fats and carbohydrates supply energy while proteins furnish certain essential components containing nitrogen and sulfur which make up a major part of human and animal cellular protoplasm.
25 Hydrolysis of protein yields substances of definite composition and structure which belong to a class of compounds called the alpha-amino acids. This process is accomplished by cleavage of the peptide bonds by an acid or a base, or by a proteolytic enzyme to simpler
30 units of proteases, peptones, polypeptides and the final building blocks of the protein molecule, the amino acids (hawk, "Practical Physiological Chemistry" 13 ed., 1954).
Hydrolytic and enzymatic degradation of the molecules, occur in the stomach, duodenum and jejunum with 35
some degradation also occurring in the ileum. Microbial degradation occurs in the ileum and colon. Complexation and mucin binding occur in the stomach, duodenum and jejunum. Passive diffusion and active transport occur in all of these digestive organs.
The general formula of an amino acid is:
R - CH2 - C - OH
1.0 NH2
wherein the R radical determines the name and characteristics of the amino acid. The principal amino acids are glycine, alanine, valine, leucine, isolucine, - -. serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, arginine, cysteine, cystine, methionine, phenyalalanine, tyrosine, tryptophan, histidine, proline and hydroxyproline.
Ashmead, et al., U.S. Patent No. 4,020,158,
2.0. describes chelate compositions which permits an increase in metal content of biological tissues. According to Ashmead, et al., protein hydrolysates are prepared in either acidic or basic media to a polypeptide, peptide or amino acid stage prior to mixing with the metal salt to
25 form the proteinate, and the pH is adjusted to a point that is sufficiently basic to remove interferring protons from both the a ine groups and the carobxyl groups. A pH of at least 7.5 and preferrably from ph 8 to pH 10 is specified by Ashmead, et al. An example given by Ashmead,
10 et al., specifies acid hydrolysis of soy protein at 130°C followed by pH adjustment of pH 8.5 for chelation.
In contrast, in the present invention, the hydrolysis is carried out a low temperature and neutral pH, resulting in a hydrolyzed protein chelate which is
35 more bioavailable for absorption and assimilation by the cells
and tissues of the body and nutritionally more beneficial than the metal compositions of the prior art.
Another method of chelation which is described is the enzymatic chelation process. Formulation of a chelate signifies a ring of atoms closed-up by holding a given atom, usually a heavy metal such as copper, zinc, iron, etc. in a molecular claw. The ligands that are formed by such a process is a function of the formation of negatively charged amino groups.
For example, the chemical process of chelation of a zinc molecule results in the formation of bonds between the amino and carboxyl groups of the amino acid with the zinc molecule in the form of a "claw" to make it more stable. This stable, water soluble metal chelate can act as a sequestering agent to facilitate the absorption of the metal rather than its removal from the system by extraction or precipitation.
Certain functional groups of compounds possess or enhance some biologic activities when incorporated in other organic molecules, as in the design and formulation of hydrolyzed protein chelates. In designing such a structure for the distinctive treatment of a specific condition of a disease or malfunction of a cell, tissue or organ, the chemist and histopharmacologist must develop a quasi-empirical method of approach. The chemist must determine the intermolecular reactions of the various compounds mixed together in a certain formula while the histopharmacologist determines the relative activity, site of absorption, and undue process of benefits and side effects of such an end product.
The method of the present invention comprises preparing food supplements using the steps of hydrolyzing protein at a pH of not less than 7.0 and not greater than 7.4 at approximately normal room temperature and reacting
the hydrolyzed protein with a mineral nutrient. The mineral nutrient is a biologically compatible compound of calcium, magnesium, iron, zinc, copper, vanadium, cobalt or manganese. The hydrolyzing step is, in a preferred embodiment, hydrolyzed by a proteolytic enzyme, such as pepsin. Hydrolysis of the protein and reaction with the mineral to form the chelate may be carried out stepwise or simultaneously.
Description of the Preferred Embodiment
(L). Non-Acidic Chelation;
In chelate formulation described herein, the formula is designed knowing the physiological, pharmacological and anatomical impact upon the oral dosage form as it travels in the recipient organism before its target cell. Technology revealed herein represents a unique and sophisticated method of manufacturing chelates. The preferred route of administration for minerals is the oral. As a direct consequence of this method of administration, the dosage form is exposed to a wide variety of chemicals, enzymes, and mucin that are secreted by the gastro-intestinal tract. The pH is of utmost importance in determining both the process of absorption as well as the specific in vivo absorption site. Some substances are hydrolyzed in the acidic pH of the stomach while other carboxy.lic acid salts are precipitated as free acids. For maximum absorption it is necessary that the mineral nutrient be in solution. The solubility factor must be optimum because if it is too soluble it is rapidly excreted through the kidneys, and if insoluble, absorption does not occur and excretion occurs via the gastro-intestinal tract. pH requirements for absorption in the various parts of the gastro-intestinal tract are shown in Table I.
Anatomical Length Diameter Villi pH
Unit (cm) (cm) Present
Mouth 15-20 10 No 6.4
Esophagus 25 2.5 No 5.6-6.0
Stomach 20 15 No 1.0-3.0
Duodenum 25 5 Yes 5.0
Jejunum 300 5 Yes 6.0-7.0
Ileum 300 2.5-5. 0 Yes 7.6
Lg. Intestine 200 2.5-7. 0 No 7.5-8.0
A base is defined as a compound which yield negatively charged hydroxyl ions in solution. For pure water every hydrogen ion set free a hydroxyl ion must be liberated so that the concentrations of the two ions remain equal i.e. [H ] = [OH-]. The value of K at 25°C is 1 x 10 ~14 i.e. [H+] x [OH-] = 1 x 10 ~14 and since pH = -log [H ] then the pH is 7.0 or neutral.
Since the pH is the negative logarithm of the hydrogen ion concentration and the product of the [H ] and [OH ] ion concentrations is constant at 1 x 10 , the optimum pH for the formation of a genuine amino acid chelate is 7.0^ 0.05, i.e. neutral.
The isoelectric points of proteins are very significant because at this point the properties of the protein undergo unique changes. In solutions acid to their isoelectric points they become positively charged ions, capable of combining with negative ions to form salts, while in solutions alkalline to their isoelectric points proteins exist as negatively charged ions which can combine only with positive ions (Hawk, Practical Physiological Chemistry, 13th ed., 1954 P. 166). Since chelates are not salting out molecules, and unlike the prior art, the pH is maintained at a neutral level of 7.0, just like water, because at the isoelectric point the
protein used in the chelation process behaves as though it is a zwitterion. This is achieved by measuring the pH of the protein which in case of gelatin for example is 4.80 and that of caseine 4.55 and increasing it by using 0.1 N sodium hydroxide to a neutral pH of 7.0.
Ashmead, et al., recommended the use of pH 8-10 and went down as far as 7.5, at this level the. process of Ashmead creates a salt and not a chelate. This does not take into consideration the facilitative absorption mechanism achieved by this invention. The intracellular fluid of the cells is very much different than the extracellular fluid (Guyton, A. , Basic Human Physiology, 1971, P 37). The extracellular fluid contains large quantities of sodium 142 meq/1 while the intracellular fluid contains only 10 meq/1. The pH of the intracellular fluid is 7.0 while that of extracellular fluid is 7.4. Positively charged ions, such as sodium and potassium pass through the cell membrane with difficulty, because of the presence of positive charges of proteins or absorbed positive ions such as calcium "ions lining the pores. In contrast negatively charged ions pass through the mammalian cell membrane pores much more easily. All these factors are interelated to the concentration gradient which is pH dependent, and this is of major importance to the red blood corpuscles. The amount of osmotic pressure caused by a solute is proportional to the concentration of the solute in numbers of molecules. At normal body temperature a concentration of 1 osmol per liter will cause 19,300 mm Hg osmotic pressure in the solution, (Guyton A., Basic Human Physiology, 1971, p. 43). That is why it is very important to maintain the pH to 7.0 - 7.4 and not more in order not to risk the occurance of hemolysis and to shift the balance of homeostatis, where acidosis occurs at pH lower than 7.0 and alkalosis at pH higher than 7.4.
Isolated proteins either from soy, barley,
gliadin, corn protein or gluten, wheat gluten, potatoe or peanut meals or milk derivatives such as casein, hydrolyzed casein are mixtures of various reactive amino acids. Basic hydrolysis leaves the individual amino acids exposed with the positively charged amino groups and negatively charged carboxyl groups available to be attached by the cleaved salt of a metal forming a positively charged metal and a water molecule. The pH of the resulting chelate which is slightly acidic is adjusted by 0.1 N sodium hydroxide to 7.0. The stability constant is then determined by the concentration of the chelate that is formed compared to the concentration of the reacting chemicals. This factor determines the degree of catabolism of the amino acid chelate at the site of its target organ.
This new and innovative non-acidic chelation process is not a salting-out procedure dependent on the concentration of the mineral salt and the protein concentration, rather, it is an electro-chemical process depending on the valancy of the metal and the availability of the amino acid. Since the heat is generated only from the chemical reaction, the process of the present chelation method is an endogenous endothermal, low heat mechanism. In contrast, the method of the prior art employs a heating process up to 130°C, and a very basic pH to activate the metal ion into dissociation and reactive binding with the available amino acid carboxyl groups of the amino acid. To illustrate with an example:
A multi mineral chelated tablet for oral dosage is manufactured by the following:
10,000 tablet batch
POTENCY EACH TABLET CONTAINS: KG
100 mg Calcium Carbonate = 40 mg Calcium
100 mg Magnesium Oxide = 60 mg Magnesium
100 mg Ferrous Fumarate
= 32 g Iron
100 mg Zinc Sulfate = 23 mg Zinc
Barley Protein Isolate
Sodium Hydroxide (0.1N) q.s. to pH 7.0
The procedure involves mixing the mineral salts in a wet mixer - granulator for 20-30 minutes, then adding the barley protein isolate and mixing for another 20 minutes.
The mix is then wetted with deionized distilled water to a slurry-like texture;, the pH is measured which is usually slightly acidic about 6.0, then adjusted to pH 7.0 with 0.1N sodium hydroxide, using water as the wetting agent as the need may be to a final wet mix. The material is spread on trays, dried in an oven to 25°C for 3 days, ground up, mixed with excipients and tabletted according to certain preset specifications.
Infra-red spectroscopic tracings of the multi-mineral hydrolyzed barley protein chelate shows very prominent and conspicuous abosrption peaks completely different than the tracings of the individual metal salts used as starting materials in the chelating process.
The same process applies to single metal amino acid chelates, using 25% of the total amount of the salt for the protein amount and adjusting the pH with 0.1N sodium hydroxide to 7.0 using deionized, distilled water as the wetting agent, to get a uniform wet mixture.
(2) Enzymatic Chelation
Another method of chelation we are describing, that no previous art has discussed is the enzymatic chelation process. Hydrolysis of a protein can be achieved by the action of an acid, base or enzymes. If a protein contains a tryptophan molecule, acid hydrolysis would destroy it completely and alkaline hydrolysis might cause a reacemization process. In general, enzymatic digestion of proteins is the most suitable method of hydrolysis for oral ingestion, and is more advantageous over the other types of hydrolysis since it causes the cleavage of the peptide bonds without subjecting the protein molecule to the shearing effect of the acid or base used in the other chelation processes.
Enzymes are very effective in small amounts and they remain unchanged after the reaction takes place, but the drawbacks to this process is the sensitivity of the enzyme to temperature, pH, and salt concentrations which affect their stability and the cost for its commercial application since the enzymes are very expensive to buy and maintain their activity. The ionization state which affects the activity of the enzyme is pH dependent; thus, the enzymatic chelation process is pH sensitized. The enzymatic chelation process depends on two factors:
1. The time required for the enzyme to combine with the substrate , which is the protein in this case, to cause the availability of the amino acid molecules.
2. The time required for the metal ion to combine with the free amino acids to form the chelate.
The higher the substrate concentration the shorter will be the time.
Each chemical reaction reaches its equilibrium as illustrated by such a formula:
A + B«=→C + D Forward and backward reactions are equal when equilibrium is reached.
Since enzymes act as catalysts they increase the speed of the reaction to reach equilibrium. This can be expressed by an equation according to the law of mass action which states that the reaction rate is proportional to the product of the concentration of the reactants:
*-^r = Kχ [A] x [B] and λ
-^*= K2 [C] x [D] 2 where K. and K~ are equilibrium constants and V is the velocity of the reaction. In order for the reaction to be reversible then:
1 λ* 2 Δ or
Kχ [A] x [B] = K2 [C] x [D] which transforms to:
where K is the equilibrium constant. In the enzymatic chelation method an equilibrium constant is achieved when the concentration ratio of the reactants is at equilibrium.
The K depends on the pH and temperature to get a full range amino acid chelation. In the present process pH is optimize at 7.0 and temperatures at 25°C, which is low heat, endo-thermal, to form a biologically active hydrolyzed protein chelate, that can be easily absorbed and assimilated through the gastro-intestinal tract.
A zinc sulfate molecule dissociated into zinc and sulfate molecules that are positively and negatively charged respectively
ZnSo-4 .Zn ++ + So: To obtain a genuine full range enzymatic amino acid chelate two principles are considered in the present process:
1. Enzymatic Activity: This is measured by determining the amount of substrate ion converted per unit time.
2. Metabolite Concentration
The enzyme for which the metabolite is a substrate dictates that the reaction goes to completion in which case the metabolite is converted completely.
An illustration 'of the formation of an enzyme-s.ubstrate complex is as follows:
E + SFS E + P
E = Enzyme S = Substrate P= Reaction Product
Enzyme reactions are associated with cellular membranes. Sugars are transported into yeast cells by a mechanism involving phosphorylatin by enzymes located in the cell surface. That is to say that newly formed enzymes contain carbons arising from amino acids synthesized subsequent to addition of an inducer and utilization of the individual amino acids is simultaneous, rather than by stepwise synthesis of longer chain molecules. With this principle in mind, it is relevant to recall that minerals may activate enzyme formation and separation by forming chelates or complexes, with different kinds of proteins. Magnesium interacts with
purines and pyrimidines to form chelate rings, which in turn may become part of enzyme systems, for example.
The following is exemplary of the method which may be utilized in practicing the invention. The preparation of a calcium/magnesium chelate as an oral dosage with the following concentrations is described:
10,000 tablet batch POTENCY EACH TABLET CONTAINS: KG
250 mg Calcium Carbonate 2.5
=100 mg Calcium
166.66 mg Magnesium Oxide 1.660
=100 mg Magnesium
Calcium carbonate and Magnesium Oxide are mixed thoroughly with deionized distilled water, to a wet finish and kept in a mixer. 1.040 Kg of soy protein isolate which is 25% by weight of the salt mix is wetted with dionized, distilled water, the pH is adjusted to 7.0 with 0.1N sodium hydroxide and an equal amount of Pepsin N.F. powder is mixed with it, spread on trays and put in an oven at 25 C for 18 hours. The hydrolyzed soy protein is then added to the Calcium/Magnesium wet mix, deionized distilled water is added if the need may be, mixed thoroughly for about 30 minutes and spread on trays and let to dry in an oven at 25°C for about three days. The dry material is oscillated, mixed with excipients and tableted according to conventional specifications.
An infra-red spectroscopic tracing between the final Calcium/Magnesium chelate and the single ingredients of Calcium Carbonate and Magnesium Oxide shows the peaks of absorption to be entirely unique and different proving the formation of a new compound of Calcium and Magnesium hydrolyzed protein chelate.
The same procedure applies to single mineral salts. Other adequate proteolytic enzymes could be used besides the pepsin.
The knowledge of intermolecular and intramolecular binding forces is very important and essential in the manufacture of genuine full range chelates. The electrostatic attraction of dipole interaction between a negatively charged and positively charged molecules from what is known as Van Der Waals forces is important to know which elements can form chelates or proteinates or complexes.
Calcium, magnesium, vanadium, manganese, copper, cobalt, iron and zinc are metals which various valancies in the periodic chart can be chelated and rendered bioavailable to the cellular epithelium. Selenium, although belongs to the non-metal group with three different valancies it can be bound biologically to yeast by an enzymatic process. In contrast chromium belongs to the metal group with valancies of 2, 3 and 6, yet can be biologically bound to yeast by an enzymatically active process or geniunely chelated.
All these processes of chelating the metals, such as chromium, selenium, lithium, etc., proteinating the potassium or complexing the phosphorus require energy for preparation or for absorption. The metabolism of a protein may be said to involve all the changes which occur in that protein during ingestion, digestion, absorption, transport, storage, utilization, synthesis, conversion to carbohydrate and in fact, breakdown and excretion. Digestion of the protein begins in the stomach and continues in the intestine under the influence of proteolytic enzymes until it is broken down into amino acids. Since the metal in the chelate forms have no electro-chemical positive charge, the active transport mechanism that occurs through the intestinal villa and cellular mucosa is facilitated to increase the bioavailability of the elements to the tissues. Minerals are usually activators of enzyme synthesis or formation processes and in accord with the
law of equilibrium of aqueous solutions, diffusion of solvent occurs from the hypotonic to the hypertonic medium which is influenced by the presence of other ions which compete for a position in the membrane surface causing a competitive inhibition process of some elements that are crucial to the metabolism of the cell. Under properly controlled conditions it was shown that various amino acids are transported in descending order of efficiency as follows: L-Valine, L-Alanine, Glycine, L-Arginine, dl-Phenylalanine. This entices one to take into consideration the type of protein to use in forming chelates, knowing the absorption coefficient of each. Some people are allergic to soy derivatives, others are allergic to milk derivatives. In choosing the amino acid source for a chelation process, one decreases the hypoallergenicity of the various foreign particles present by exposing the medium to an electro-neutral agent such as suitable base in a water solution as noted before -_.o precipitate the allergents and form a chelate that is neuroallergenic. The higher the protein efficiency ratio the higher effectiveness of the chelation process would be. Soy protein isolate has a protein efficiency ratio of 2.1, while that of lactalbumin is 4.7, and barley protein isolate of 2.0. The endo-thermal, stable genuine hydrolyzed protein chelate is far more superior in its benefits, when it is prepared according to this new innovative method, compared to its properties when prepared according to the prior arts . Industrial Application
This invention is useful in the manufacture of food supplements for human and animal useage.
Claims
1. The method of preparing food supplements comprising the steps of (a) hydrolyzing protein at a pH of not less than 7.0 and not greater than 7.4 at approximately normal room temperature and (b) reacting the hydrolyzed protein with a mineral nutrient.
2. The method of Claim 1 wherein the mineral nutrient is a biologically compatible compound of calcium, magnesium, iron, zinc, copper, vanadium, cobalt, manganese, chromium, selenium, lithium or germanium.
3. The method of Claim 2 where in the hydrolyzing step is catalyzed by a proteolytic enzyme.
4. The method of Claim 3 wherein the enzyme is pepsin.
5. The method of Claim 1 wherein the hydrolyzing step is catalyzed by a proteolytic enzyme.
6. The method of Claim 5 wherein the enzyme is pepsin.
7. The method of Claim 1 where in the mineral nutrient is reacted with the protein during the step of hydrolyzing the protein to form a full range amino-acid chelate.
8. A food supplement consisting essentially of protein which has been hydrolyzed at a pH of not less 7.0 and not greater than 7.4 at approximately normal room temperature and reacted with a mineral nutrient.
9. The food supplement of Claim 8 when the mineral nutrient is biologically compatible compound of calcium, magnesium, iron, zinc, copper, vanadium, cobalt, manganese, chromium, selenium, lithium, or germanium.
10. A food supplement consisting essentially of protein which has been hydrolyzed at a pH of not less than 7.0 and not greater than 7.4 by a proteolytic -enzyme at approximately normal room temperature and reacted with mineral nutrient.
11. The food supplement of Claim 10 wherein the mineral nutrient is a biologically compatible compound of calcium, magnesium, iron, zinc, copper, vanadium, cobalt, manganese, chromium, selenium, germanium, or lithium.
12. The food supplement of Claim 11 wherein the mineral nutrient is a biologically compatible compound of potassium proteinate phosphorus complex and other minerals.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US79787185A | 1985-11-14 | 1985-11-14 | |
US797,871 | 1985-11-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1987002867A1 true WO1987002867A1 (en) | 1987-05-21 |
Family
ID=25171996
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1986/002193 WO1987002867A1 (en) | 1985-11-14 | 1986-10-17 | Hydrolyzed protein chelates |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0245358A1 (en) |
AU (1) | AU6479686A (en) |
WO (1) | WO1987002867A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998008524A1 (en) * | 1996-08-26 | 1998-03-05 | Nicholas James Gonzalez | Multimineral products useful in achieving autonomic balance |
RU2243677C1 (en) * | 2003-07-24 | 2005-01-10 | Егиазарян Гагик Геворкович | Nutrient chelate complex |
RU2376892C1 (en) * | 2008-08-08 | 2009-12-27 | Владимир Кимович Мазо | Food chelate complex (versions) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3898160A (en) * | 1972-07-25 | 1975-08-05 | Us Agriculture | Recovering proteins from waste water |
US3969540A (en) * | 1975-09-11 | 1976-07-13 | Albion Laboratories, Inc. | Enzymatically prepared metal proteinates |
US4201793A (en) * | 1976-11-19 | 1980-05-06 | Ashmead H H | Oil cooked foods containing metal proteinates |
US4216144A (en) * | 1977-10-20 | 1980-08-05 | Ashmead H H | Soluble iron proteinates |
US4293583A (en) * | 1979-01-26 | 1981-10-06 | Societe D'assistance Technique Pour Produits Nestle S.A. | Process for debittering a protein hydrolysate and the debittered hydrolysate obtained by this process |
-
1986
- 1986-10-17 WO PCT/US1986/002193 patent/WO1987002867A1/en unknown
- 1986-10-17 EP EP19860906635 patent/EP0245358A1/en active Pending
- 1986-10-17 AU AU64796/86A patent/AU6479686A/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3898160A (en) * | 1972-07-25 | 1975-08-05 | Us Agriculture | Recovering proteins from waste water |
US3969540A (en) * | 1975-09-11 | 1976-07-13 | Albion Laboratories, Inc. | Enzymatically prepared metal proteinates |
US4201793A (en) * | 1976-11-19 | 1980-05-06 | Ashmead H H | Oil cooked foods containing metal proteinates |
US4216144A (en) * | 1977-10-20 | 1980-08-05 | Ashmead H H | Soluble iron proteinates |
US4293583A (en) * | 1979-01-26 | 1981-10-06 | Societe D'assistance Technique Pour Produits Nestle S.A. | Process for debittering a protein hydrolysate and the debittered hydrolysate obtained by this process |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998008524A1 (en) * | 1996-08-26 | 1998-03-05 | Nicholas James Gonzalez | Multimineral products useful in achieving autonomic balance |
RU2243677C1 (en) * | 2003-07-24 | 2005-01-10 | Егиазарян Гагик Геворкович | Nutrient chelate complex |
RU2376892C1 (en) * | 2008-08-08 | 2009-12-27 | Владимир Кимович Мазо | Food chelate complex (versions) |
Also Published As
Publication number | Publication date |
---|---|
EP0245358A1 (en) | 1987-11-19 |
AU6479686A (en) | 1987-06-02 |
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